Inclusion Criteria

Inclusion criteria

1. 18 years of age or older.

2. A female is eligible to enter and participate in the study if she is of:

- Non-child-bearing potential (i.e., physiologically incapable of becoming
pregnant), including any female who:

- Has had a hysterectomy, or

- Has had a bilateral oophorectomy (ovariectomy), or

- Has had a bilateral tubal ligation, or

- Is considered post-menopausal (defined as amenorrheic for greater than or equal
to 1 year).

- Childbearing potential, has a negative serum pregnancy test at Screening and
agrees to one of the following from 2 weeks prior to enrolment and continue
through the post-study visit:

- Complete abstinence from sexual intercourse

- Oral Contraceptive, either combined or progestogen alone (must use a back up
method, if have taken for less than 3 cycles)

- Injectable progestogen

- Implants of levonorgestrel

- Estrogenic vaginal ring

- Percutaneous contraceptive patches

- Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure
rate of less than 1% per year

- Male partner sterilization (vasectomy with documentation of azoospermia) prior
to the female subject's entry into the study, and this male is the sole partner
for that subject

- Double barrier method: condom or occlusive cap (diaphragm or cervical/vault
caps) plus spermicidal agent (foam/gel/film/cream/suppository)

3. Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.

4. Provided written informed consent.

5. Hemoglobin greater than or equal to 8 gm/dL (5 nmol/L), if clinically stable.

6. Absolute neutrophil count greater than or equal to 1,500/mm^3 (1.5 x 109/L).

7. Calculated creatinine clearance (CrCl) greater than or equal to 50 mls/min.

8. Total bilirubin less than or equal to 1.25 times the institutional upper limit of
normal (ULN).

9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or
equal to 2 times the ULN. For subjects with liver metastases: AST or ALT less than
or equal to 5 times the ULN.

10. LVEF greater than or equal to 50% or greater than or equal to LLN for the institution
based on multiple gated acquisition scan (MUGA) or echocardiogram (ECHO).

Specific to Phase I:

11. Recurrent, advanced, or metastatic cancer that is known to be potentially responsive
to treatment with fluoropyrimidines or oxaliplatin. Examples include
gastrointestinal tumors, HER2 (ErbB2)-positive breast cancer, and lung cancers.

12. Received less than or equal to 3 prior chemotherapy regimens without pelvic
radiotherapy or less than or equal to 2 prior chemotherapy regimens if received
pelvic radiotherapy.

13. Platelet count greater than or equal to 75,000/mm^3 (75 x 109/L).

Specific to Phase II:

14. Histologically-confirmed, measurable advanced or metastatic CRC previously untreated
in the metastatic setting or more than 6 months post an oxaliplatin-containing
adjuvant therapy.

15. Archived paraffin-embedded tumor tissue must be available for biomarker analysis.

16. Platelet count greater than or equal to 100,000/mm^3 (100 x 109/L).

Exclusion Critera:

1. Pregnant or lactating female.

2. Prior resection of the small bowel.

3. Brain metastases that require additional treatment.

4. Medically unfit for the study as a result of the medical interview, physical exam, or
screening investigations.

5. Taking any medication on the prohibited medications list (see Section 9.2).

6. History of drug or other allergy, which, in the opinion of the Investigator,
contraindicates participation.

7. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to the study drugs. These include other anilinoquinazolines, such
as gefitinib [Iressa], or erlotinib [Tarceva]. The subject has received treatment
with any investigational drug in the previous four weeks.

8. Treatment with any biologic, cytotoxic, radiation , or hormonal (other than for
contraception or replacement) therapy within four weeks. Treatment with hormones
with short half-lives is allowed up to 1 week prior to study treatment after
consultation with GSK medical monitor.

9. Major surgery within the previous two weeks unless in the opinion of the
Investigator, the subject has recovered sufficiently to begin study treatment.

10. Physiological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol.

11. Receiving concurrent coumadin therapy. Minidose coumadin for maintenance of
catheters (0.5 to 1.0 mg/day), and other anticoagulation therapy are allowed on
study. Subjects receiving minidose coumadin must have prothrombin time (PT) or
International normalized ratio (INR) and partial thromboplastin time (PTT) within 1.2
times the ULN.

12. History of uncontrolled or symptomatic angina, arrhythmias, or congestive heart
failure.

13. Corrected QT interval (QTc) greater than 450 msecs.

Specific to Phase I:

14. Residual chemotherapy related toxicity of greater than or equal to Grade 2 that is
clinically felt likely to be exacerbated by the treatment regimen.

Specific to Phase II (amendment written after the completion of Phase 1):

15. Have current active hepatic or biliary disease (with exception of patients with
Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver
disease per investigator assessment.